Fong Jordan A, Reeg Logan, Darrow Jewels, Williamson Robert H, Riordan Anna, Cash Alexia K, Beecroft Max, Fogle Callie A, Mathews Kyle G, Nelson Nathan C, Iuga Alina C, Gerber David A, Sano Michael B
Gradient Medical Inc., Raleigh, NC 27607, USA.
College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA.
Cancers (Basel). 2025 Sep 2;17(17):2891. doi: 10.3390/cancers17172891.
There is a critical need for effective focal therapies for patients with inoperable or anatomically complex tumors where conventional ablation techniques pose high risk or are ineffective. Integrated Nanosecond Pulsed Irreversible Electroporation (INSPIRE) is a novel non-thermal ablation modality which uses real time temperature feedback during pulse delivery to safely treat tumors near critical structures. This study evaluated the impact of exposed electrode length on ablation zone size, reproducibility, and cardiac safety in a large animal model. INSPIRE treatments were performed in an in vivo healthy porcine liver model. All treatments administered 6000 V 1000 ns pulses with a 45 °C temperature set point. Treatments were administered percutaneously via an electrode and grounding pad approach using an internally cooled electrode applicator. The exposed electrode region at the distal end of the applicator was set to either 0.5, 1.0, 1.5, or 2.0 cm. Ablation zones were assessed via ultrasound, contrast-enhanced CT, and gross pathology one week post-treatment. Cardiac safety was evaluated by measuring pre- and post-treatment serum Troponin levels. All treatments were completed without adverse events. Troponin levels remained stable (pre: 0.249 ng/mL; post: 0.224 ng/mL), indicating no measurable cardiac injury. The 1.5 cm exposure length produced the largest and most consistent ablation volumes, with a mean volume of 12.8 ± 2.6 cm and average dimensions of 3.7 × 2.7 cm in under 6 min. Increasing exposure length beyond 1.5 cm introduced greater variability and reduced treatment volumes. INSPIRE enables safe, large-volume, single-applicator ablation without a need for electrical pulse synchronization with R wave in cardiac rhythm. The 1.5 cm exposure length offers optimal balance between energy delivery and treatment consistency. These findings support further clinical investigation of INSPIRE for non-thermal ablation of inoperable tumors.
对于患有无法手术或解剖结构复杂肿瘤的患者,传统消融技术存在高风险或无效,因此迫切需要有效的局部治疗方法。集成纳秒脉冲不可逆电穿孔(INSPIRE)是一种新型非热消融方式,在脉冲传输过程中使用实时温度反馈来安全治疗关键结构附近的肿瘤。本研究在大型动物模型中评估了暴露电极长度对消融区大小、可重复性和心脏安全性的影响。在健康猪肝脏的体内模型中进行了INSPIRE治疗。所有治疗均施加6000 V、1000 ns的脉冲,温度设定点为45℃。通过内部冷却的电极施加器,经皮通过电极和接地垫方法进行治疗。将施加器远端的暴露电极区域设置为0.5、1.0、1.5或2.0 cm。治疗后一周,通过超声、对比增强CT和大体病理学评估消融区。通过测量治疗前后的血清肌钙蛋白水平评估心脏安全性。所有治疗均顺利完成,无不良事件发生。肌钙蛋白水平保持稳定(治疗前:0.249 ng/mL;治疗后:0.224 ng/mL),表明无明显心脏损伤。1.5 cm的暴露长度产生了最大且最一致的消融体积,平均体积为12.8±2.6 cm,在6分钟内平均尺寸为3.7×2.7 cm。将暴露长度增加到超过1.5 cm会引入更大的变异性并减小治疗体积。INSPIRE能够实现安全、大体积、单施加器消融,无需与心律中的R波进行电脉冲同步。1.5 cm的暴露长度在能量传递和治疗一致性之间提供了最佳平衡。这些发现支持对INSPIRE进行进一步临床研究,用于无法手术肿瘤的非热消融。